Sirtuins play key role in protein modifications Joel D. Brock, Cornell University, DMR 0936384

1. Sirtuins play key role in protein modificationsJoel D. Brock, Cornell University, DMR 0936384 Intellectual Merit: For some proteins, more is needed after their translation from DNA before they are functional. Small molecules are attached to certain amino acids in the protein in a process called post-translational modification. If the attachments are later removed, the behavior of the protein changes. The family of proteins called "sirtuins" is responsible for such removals in a number of biological systems. There are several members of the sirtuin family, and the majority of them catalyze the deacetylation of certain lysine amino acid residues which have been post-translationally modified by the addition of acetate. However, Sirt5, a sirtuin found in mitochondria, does not appear to work this way. Yeyun Zhou, a Cornell biophysics graduate student, used X-ray diffraction at CHESS to find out why Sirt5 is different, and what it does do instead of deacetylation. J. Du, Y. Zhou, X. Su, J.J. Yu, S. Khan, H. Jiang, J. Kim, J. Woo, J. H. Kim, B. H. Choi, B. He, W. Chen, S. Zhang, R. A. Cerione, J. Auwerx, Q. Hao, and H. Lin; "Sirt5 is a NAD-dependent Protein Lysine Demalonylase and Desuccinylase", Science 334, 806-809 (2011). Close-up of succinyl peptide and NAD bound in Sirt5, showing interactions of succinyl with Tyr 102 and Arg 105 of SirT5. CHESS DMR-0936384 2012_1